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Children deserve to be treated with appropriate medicines based on robust assessments. Despite the introduction of new regulations, the availability of medicines for children is suboptimal because of the frequent lack of relevant clinical trials due to the difficulty of conducting such trials. Thus, the Transparency Committee (TC) of the French National Authority for Health, who oversees the assessment of medicinal products in France, set up a pediatric working group with two aims: (1) The first aim was to review all opinions on medicines for pediatric use. Out of 536 opinions delivered between 2020 and 2022, 181 (34 %) concerned medicines for pediatric use. Whereas oncology largely dominated the medicines for adults, medicines for infectious diseases, endocrinology/metabolism, neurology, and hematology mostly prevailed for children. (2) The second aim was to clarify the evaluation criteria assessed by the TC, namely, the clinical benefit (CB), the clinical added value (CAV), and the public health impact (PHI) for pediatric medicinal products. An important CB was given to 113 out of 161 (71 %) opinions on medicines for pediatric use when it concerned pathologies with a severe prognosis. The quality of the demonstration (e.g., double-blind randomized trial vs. placebo or another active medicine) played a major role in the CB level. Clinical pediatric studies were also consistently associated with higher CAV levels: levels I (major) to III (moderate) in 26 out of 42 (62 %) opinions, level IV (minor) and level V (no therapeutic progress) in 43 out of 84 (51 %) and 30 out of 43 (70 %) opinions granting a sufficient CB, respectively. Conversely, 22 out of 30 (73 %) dossiers based only on literature reviews were given a level V. The main criteria leading to the qualification of a medicine for pediatric use as providing a PHI included a significant change in the morbidity and mortality of the disease and an improvement in the care pathway. Assessments were mostly aligned on the adults in the case of subsequent extensions of indications to children. Lastly, new measures were taken aimed at shortening median delays in the assessment process in order to reduce off-label use of medicines in France., Competing Interests: Declaration of competing interests None (See https://dpi-declaration.sante.gouv.fr)., (Copyright © 2024 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Cystic fibrosis is a severe monogenic disease that affects around 7400 patients in France. More than 2100 mutations in the cystic fibrosis conductance transmembrane regulator (CFTR), the gene encoding for an epithelial ion channel that normally transports chloride and bicarbonate, lead to mucus dehydration and impaired bronchial clearance. Systematic neonatal screening in France since 2002 has enabled early diagnosis of cystic fibrosis. Although highly demanding, supportive treatments including daily chest physiotherapy, inhaled aerosol therapy, frequent antibiotic courses, nutritional and pancreatic extracts have improved the prognosis. Median age at death is now beyond 30 years. Ivacaftor was the first CFTR modulator found to both reduce sweat chloride concentration and improve pulmonary function in the rare CFTR gating mutations. Combinations of modulators such as lumacaftor + ivacaftor or tezacaftor + ivacaftor were found to improve pulmonary function both in patients homozygous for the F508del mutation characterized by the lack of CFTR protein and those heterozygous for F508del with minimal CFTR activity. The triple combination of ivacaftor + tezacaftor + elexacaftor was recently shown to significantly improve pulmonary function and quality of life, to normalize sweat chloride concentration, and to reduce the need for antibiotic therapy in patients with at least one F508del mutation (83% in France). These impressive data, however, need to be confirmed in the long term. Nevertheless, it is encouraging to hear treated patients testify about their markedly improved quality of life and to observe that the number of lung transplants for cystic fibrosis decreased dramatically in France after 2020, despite the COVID pandemic, with no increase in deaths without lung transplant., Competing Interests: Declaration of Competing Interest Pierre Foucaud and Jean-Christophe Mercier declare they have no conflicts of interest related to this work., (Copyright © 2022. Published by Elsevier Masson SAS.)

Intravenous fluids are frequently used in hospitalized children. Hypotonic fluids have been the standard of care in pediatrics for many years. This might be explained by the empiricism of early recommendations favoring fluids with dextrose, but an insufficient amount of sodium. The risk of hyponatremia (<135mmol/L) might be increased by the occurrence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in the course of common acute diseases (e.g., bronchiolitis, acute gastroenteritis, encephalitis, meningitis) in children. Severe hyponatremia (<130mmol/L) is often associated with neurologic complications leading to sequelae or even death. Over the last few years, hyponatremia induced by hypotonic fluids has been increasingly reported, and significant progress has been made in the understanding of cerebral edema and osmotic demyelination. Several randomized clinical trials have shown weak but significant evidence that isotonic fluids were superior to hypotonic solutions in preventing hyponatremia. However, clinical practices have not changed much in France, as suggested by the analysis of intravenous fluids ordered from the Assistance Publique-Hôpitaux de Paris (AP-HP) central pharmacy (PCH) in 2017. Therefore, it would be advisable that national guidelines be released under the French Health Authorities regarding the safe infusion of infants and children., (Copyright © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Suicide attempts (SA) in children are often considered rare and poorly studied. The aim of this study was to explore the clinical characteristics of SA in children under 12 years of age. A retrospective assessment was conducted in 30 consecutive SAs reported in children under 12 years of age admitted to the emergency department at the Robert-Debré University Hospital (Paris, France) from 2007 to 2010 and the Regional University Hospital (Besançon, France) from 2000 to 2008. All suicide attempters were directly assessed at the somatic and psychiatric level. Patients were 8-11 years old (mean, 10.2±0.8). The sex ratio was 0.9 boys for 1 girl. The leading SA methods were poisoning by medication (53.3%), hanging or strangulation (23.3%), jumping from a height (16.7%), poisoning by chemicals (3.3%), and lesions inflicted by sharp objects (3.3%). In addition, SAs were characterized by high lethality (43.7%) contrasting with their low to moderate suicidal intentionality (43.8% and 56.2%, respectively). In conclusion, we reported that SA in children differs from those of adolescents by their greater lethality related to the methods used, but contrasting with the low intentionality mentioned by these patients., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Objectives: Evaluating the frequency and modalities of transmissible infection prevention counseling in children before a stay in tropical or subtropical areas., Methods: Description of the frequency and modalities of transmissible infection prevention counseling (except specific vaccination) given prior to travel in children attending a tertiary care center in Paris, France, for fever occurring within 3 months following a return from Africa. Data were collected retrospectively from medical observations and telephone interviews with parents., Results: A total of 173 children were included; 98 and 75 returned from sub-Saharan Africa and North Africa, respectively. Forty-one percent were less than 2 years old. Eighty-one percent of the children had consulted before leaving. Among children who returned from North Africa, the proportion of children who had a specific preventive consultation before travel was lower than among children who returned from sub-Saharan Africa (respectively, 72.1% versus 94.7%; p<0.001). In children having consulted before traveling, specific hygiene and diet advice had been given in 72% of cases but less frequently in children who traveled in North Africa compared to children who traveled to sub-Saharan Africa (respectively, 57.8% vs. 92.2%; p<0.001). Among children who returned from North Africa, those who had no preventive consultation before travel had febrile gastrointestinal infection more frequently than those who had a consultation before traveling (p=0.003)., Conclusion: Although in this study the majority of children traveling to Africa receive transmissible infection prevention counseling before the travel, prevention could be improved, particularly before a stay in North Africa., (Copyright © 2011. Published by Elsevier SAS.)

With the advent of prenatal steroids, postnatal exogenous surfactant and less aggressive respiratory support, premature infants can develop chronic lung disease without even acute respiratory distress. This "new bronchopulmonary dysplasia" could be the result of impaired postnatal growth. Several experimental studies have suggested a possible role of the vascular endothelial growth factor/nitric oxide (VEGF/NO) pathway in restoring pulmonary angiogenesis and enhancing distal lung growth. The results of the clinical studies are, however, inconclusive, and it is currently unclear which subsets of premature infants might benefit from inhaled nitric oxide. Besides, severe intracranial haemorrhage and/or cystic periventricular leukomalacia may affect the most immature babies, many of whom are spared from severe initial respiratory disease. Recently, inhaled nitric oxide was shown to significantly decrease the incidence of these neurological events, and to improve the long-term outcome in a few clinical trials. At times neuroprotective, at times neurotoxic, nitric oxide is capable of divergent effects depending upon the extent of cerebral damage, the redox state of the cell, and the experimental model used. Recently, inhaled nitric oxide had recognized to have dramatic remote effects including angiogenesis and maturation on the developing brain in rodent pups. Therefore, the developmental consequences of inhaled NO should be further investigated to ensure its safety on the developing brain and to test its potential neurprotective effect.

Despite significant progress in intensive care medicine, the mortality of septic shock has not changed in recent years. Early recognition of subtle signs in favor of meningococcal sepsis, early antibiotic treatment, and aggressive hemodynamic support remains the cornerstone of therapy of severe meningococcal shock in children. Recent work has emphasized the role of genetic polymorphisms in various systems to explain the most severe cases: anti-inflammatory cytokine profile IL-10/TNF-alpha, elevated levels of plasminogen activator inhibitor type-1, variants of the gene for mannose-binding lectin complement pathway. This may explain the disillusionment of pediatric intensivists, and the general failure of immunotherapy for sepsis. Reasonable hope lies upon new meningococcal vaccines.

Unlabelled: New issues have arisen in pediatric intensive care units, especially concerning long-stay patients. The aims of the present study were to describe the etiologic factors of these long-stay patients and to recognize the comorbidities., Material and Methods: Ninety-five patients who had a total of 100 hospitalizations of more than 30 days were admitted to the pediatric intensive care unit at Robert-Debre Hospital during a 3-year period (1993-1995); this accounted for 9.1% of total admissions. We retrospectively reviewed these 100 long-stay hospitalizations., Results: Most of these patients were newborns (65%). Patients with severe congenital anomalies (44 patients) and very premature infants (26 patients) constituted the majority of long-stay patients. The mean duration of mechanical ventilation for the 95 patients was 110 days (ranges 17-789 days). Two factors of comorbidity were found: gastroesophageal reflux (41% of cases) and nosocomial infections (89% of cases)., Conclusion: In order to prevent long stays, pediatric intensive care units must be directed toward these factors.

Despite major insights into the pathogenesis and pathophysiology of congenital diaphragmatic hernia, and despite the availability of an antenatal diagnosis and continuous progress in neonatal intensive care, little improvement has been obtained in the prognosis of this malformation. Thus obstetricians, neonatologists and pediatric surgeons are still facing a several dilemma: dilemma before birth to predict the prognosis, i.e., to evaluate the severity of the associated pulmonary hypoplasia in order to decide whether or not to interrupt pregnancy; dilemma after birth in case of severe respiratory failure to decide how far to go in life support. Based on a review of the literature and their own experience, the authors attempt to recapitulate the perinatal management and outcome of this severe malformation.

Described for the first time in 1848 by Bochdalek, congenital diaphragmatic hernia is still a hot topic. How can it be that a simple defect of the diaphragm still has a mortality rate reaching 50% in 1997, and this despite continuous progress in neonatal intensive care? If some problems remain unsolved, experimental studies over the past 30 years have raised some questions concerning the pathogenesis, and have shed some light into the pathophysiology of congenital diaphragmatic hernia. This article reviews the recent knowledge about the aetiology, pathogenesis and pathophysiology of this complex malformation.

Fetal pulmonary circulation is characterized by high resistance and low pulmonary blood flow. Right-to-left shunting through the foramen ovale and/or patent ductus arteriosus is necessary to perfuse the placenta and insure fetal life. At birth, pulmonary arterial blood flow increases immediately by 8- to 10-fold, and allows pulmonary gas exchange and postnatal life. In some circumstances, this adaptation to extra-uterine life is inadequate, because of persistent high pulmonary resistance (PPHN). Due to the lack of a selective pulmonary vasodilator, the treatment of this syndrome remained purely symptomatic using high oxygen levels and barotraumatic mechanical hyperventilation. When this medical treatment failed, the only alternative was extracorporeal membrane oxygenation (ECMO). The discovery of the major role of various endothelium-derived factors including nitric oxide (NO) in the control of vascular reactivity led to dramatic switches in the concepts of severe neonatal respiratory failure and the therapeutic approach of PPHN. It was shown, first in experimental animals then in a few infants with hypoxemic respiratory failure, that NO inhalation selectively vasodilated the vasoconstricted pulmonary vessels, and reversed right-to-left shunting and refractory hypoxemia. Whether inhaled NO also reduces mortality and/or morbidity in hypoxic infants remains to be proven by appropriate randomized clinical trials. However, not only PPHN is associated with pulmonary diseases of various etiologies and underlying pathophysiologic mechanisms, but also inhaled NO is used in conjunction with other validated therapeutic strategies including ante- or postnatal steroids, exogenous surfactants, and high-frequency oscillatory ventilation. Thus, the relevant primary endpoint might be not only crude survival but the most physiological and economical way of obtaining it.

Pulmonary vascular endothelium synthesizes and releases two groups of vasoactive substances, namely the endothelium-derived relaxing and contracting factors. Among the former, the effects of nitric oxide (NO), formerly known as endothelium-derived relaxing factor (EDRF), and those of the so-called endothelium-derived hyperpolarizing factor (EDHF) have been extensively investigated. Among the latter, endothelin is probably one of the most potent endogenous vasoconstrictors. NO is a free radical which can be readly inactivated by hemoglobin. NO has all the characteristics of a gas, whereas its pharmacological properties are consistent with those of an endogenous nitrovasodilator. Therefore, inhalation of the gas NO is now considered as one of the most promising means to treat persistent pulmonary hypertension of the newborn. EDHF relaxes vascular smooth muscle through activation of ATP-dependent potassium channels. Both the chemical nature and the physiological role of EDHF are still unclear. The pharmacological properties of endothelin are far from being unequivocal. It is a potent vasoconstrictor, when it directly acts on vascular smooth muscle. However, it can also induce the release of NO and EDHF, hence causing vasorelaxation. These effects of endothelin are mediated by various transduction pathways. Activations of ET-B receptors located on endothelium on the one hand, and ET-A receptors located on smooth muscle on the other hand, are responsible for relaxation and constriction of vascular smooth muscle, respectively. Such highly complex cellular mechanisms highlight the need for further insight into the physiology of the cell related to the pulmonary circulation. This, in turn, will help to better define the target upon which one can try to correct the abnormal function of the cell underlying the pathophysiological processes.